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1043 Comparing Older Matched Related to Younger Matched Unrelated Donors in Acute Myeloid Leukemia in Remission Using Post-Transplant Cyclophosphamide

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Expanding the Donor Pool
Hematology Disease Topics & Pathways:
Biological therapies, AML, Acute Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Transplantation
Monday, December 11, 2023: 5:30 PM

Simona Piemontese1*, Myriam Labopin2*, Goda Choi, MD3*, Annoek E.C. Broers4*, Ellen Meijer5, Gwendolyn Van Gorkom6*, Montserrat Rovira, MD, PhD7*, Maria Jesús Pascual8*, Simona Sica9*, Jan Vydra10*, Aleksander Kulagin11*, Alexandros Spyridonidis12*, Arnon Nagler13*, Ali Bazarbachi, MD, PhD14, Bipin N. Savani, MD15, Eolia Brissot16*, Jaime Sanz17*, Mohamad Mohty, MD, PhD16 and Fabio Ciceri18,19*

1Hematology and Bone Marrow Transplant Unit, San Raffaele Hospital, Milano, Milano, Italy
2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
3University of Groningen, University Medical Center Groningen (UMCG), Groningen, Netherlands
4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
5Department of Hematology, VU Medical Center, Amsterdam, Netherlands
6University Hospital Maastricht, Maastricht, Netherlands
7Hospital Clínic de Barcelona, Barcelona, Spain
8Hematology, Hospital Regional de Málaga, Malaga, Spain
9Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
10Institute of Hematology and Blood Transfusion, Prague, Czech Republic
11b. First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St-Petersburg, Russia, St. Petersburg, RUS
12Department of Internal Medicine, Bone Marrow Transplantation Unit, University Hospital of Patras, Patras, Greece
13Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel
14American University of Beirut Dept. of Medicine, Beirut, Lebanon
15Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
16Hôpital Saint-Antoine, Sorbonne University, INSERM UMRs 938, Paris, France
17Hematology Department, Hospital Universitari i Politècnic La Fe, VALENCIA, ESP
18Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, Milano, Italy
19Vita-Salute San Raffaele University, Milan, Italy

Backgroud. Over the past 25 years, the landscape of allogeneic stem cell transplantation (allo-SCT) changed from being rarely performed in patients 50 years or older to accounting for a little less than half of the transplantations reported in USA and Europe. Older patients will on average have older matched related siblings (MRD) being considered as donors with issues such as comorbidities, risk of clonal haematopoiesis of indeterminate potential, and impaired immune and regenerative potential of stem cells. Although younger HLA-matched unrelated donors (MUD) are an important alternative in this context, it remains unclear whether the use of MUD is associated with better outcomes. This is especially true in the context of post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis.

Methods. The aim of this study was to compare the graft-relapse-free survival (GRFS) for patients diagnosed with acute myeloid leukemia (AML) in first complete remission (CR1), aged 50y or more, and having received a first allo-SCT from a 10/10 MUD younger than 40y or a MRD older than 50y using PTCy for in-vivo T-cell depletion. All transplants were performed between 2015-2021 at the EBMT centres.

Results. A total of 410 consecutive patients were included, 172pts receiving a MRD, 238pts transplanted from a MUD. All patients with detailed conditioning regimen dosages were classified according to the transplant conditioning intensity (TCI) score in low (1-2), intermediate (2.5-3.5), high (4-6). TCI-score was available for 345 patients and was as follows: low in 53pts (36.8%), intermediate in 79pts (54.9%) and high in 12pts (8.3%) for MRD, low in 91pts (45.3%), intermediate in 93pts (46.3%) and high in 17pts (8.5%) for MUD (p=0.26). Only patients with available TCI-score were analysed. In univariate analysis the 2-year GRFS was 58% (49.8-65.3%) for TCI intermediate-high and 43.1% [34.3-51.5] for TCI low (p=0.005). In TCI-score intermediate-high non-relapse mortality (NRM) wasn’t higher compared to TCI-score low (12.7% [12.2-24] vs 13.7% [8.4-20.3], p=0.53) but relapse incidence (RI) was lower (17.7% [12.2-24] vs 33.2% [25.1-41.5], p=0.003). As a strong interaction between TCI-score and type of donor was found, we compared transplant outcomes between MRD and MUD separately for TCI-score low and TCI-score intermediate-high. In TCI-score low, 2-year GRFS was 44.4% [33.5-54.8] for MUD and 40.9% [26.4-54.9] for MRD (p=0.83) (Figure 1A). In multivariable analysis (MVA) type of donor was not a risk factors for neither GRFS (HR 0.98, CI: 0.57-1.69; p=0.95) nor for any other transplant outcome. In TCI-score intermediate-high, 2-year GRFS was 67.2% [55.8-76.2] for MUD and 46.1% [34.4-57.1] for MRD (p=0.001) (Figure 1B). In MVA MUD were associated to better GRFS (HR 0.41, CI: 0.24-0.7; p=0.001), lower NRM (HR 0.19, CI: 0.07-0.55; p=0.002) and lower RI (HR 0.32, CI: 0.14-0.73; p=0.007) without advantages in terms of neither aGvHD nor cGvHD.

Conclusions. In patients with AML in CR1, aged 50y or more and receiving a conditioning regimen with TCI-score ≥ 2.5 in the PTCy setting, a MUD younger than 40y is associated to longer GRFS, lower NRM and lower RI compared to a MRD older than 50y. For patients receiving regimens with TCI-score low transplant outcomes are independent on the type of HLA-matched donor.

Disclosures: Kulagin: Alexion, AstraZeneca Rare Disease, Apellis, Sobi and Generium: Honoraria, Research Funding. Savani: Takeda Development Center Americas, Inc. (TDCA): Current Employment. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding. Ciceri: ExCellThera: Other: Scientific Advisory Board .

*signifies non-member of ASH